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Patient Derived Cell Culture and Isolation of CD133+ Putative Cancer Stem Cells from Melanoma
Published on: March 13, 2013
Cell division cycle-associated protein 1 as a new melanoma-associated antigen
Aki Tokuzumi1, Satoshi Fukushima1, Azusa Miyashita1
1Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Abstract:
Immune checkpoint inhibitors have increased the median survival of melanoma patients. To improve their effects, antigen-specific therapies utilizing melanoma-associated antigens should be developed. Cell division cycle-associated protein 1 (CDCA1), which has a specific function at the kinetochores for stabilizing microtubule attachment, is overexpressed in various cancers. CDCA1, which is a member of cancer-testis antigens, does not show detectable expression levels in normal tissues. Quantitative reverse transcription polymerase chain reaction and immunoblotting analyses revealed that CDCA1 was expressed in all of the tested melanoma cell lines, 74% of primary melanomas, 64% of metastatic melanomas and 25% of nevi. An immunohistochemical analysis and a Cox proportional hazards model showed that CDCA1 could be a prognostic marker in malignant melanoma (MM) patients. CDCA1-specific siRNA inhibited the cell proliferation of SKMEL2 and WM115 cells, but did not reduce the migration or invasion activity. These results suggest that CDCA1 may be a new therapeutic target of melanoma.
Insights
Cell division cycle-associated protein 1 (CDCA1) is overexpressed in melanoma and may serve as a prognostic marker. Targeting CDCA1 could offer a new therapeutic strategy for melanoma patients.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Immune checkpoint inhibitors have improved melanoma survival rates.
- Antigen-specific therapies targeting melanoma-associated antigens are needed to enhance treatment efficacy.
- Cell division cycle-associated protein 1 (CDCA1) is a cancer-testis antigen overexpressed in various cancers, including melanoma.
Purpose of the Study:
- To investigate the expression and prognostic significance of CDCA1 in melanoma.
- To evaluate the potential of CDCA1 as a therapeutic target in melanoma.
Main Methods:
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunoblotting were used to assess CDCA1 expression in melanoma cell lines, primary melanomas, metastatic melanomas, and nevi.
- Immunohistochemical analysis and Cox proportional hazards modeling were employed to determine the prognostic value of CDCA1.
- CDCA1-specific small interfering RNA (siRNA) was used to assess its effect on melanoma cell proliferation, migration, and invasion.
Main Results:
- CDCA1 was expressed in all tested melanoma cell lines, 74% of primary melanomas, 64% of metastatic melanomas, and 25% of nevi.
- CDCA1 expression was significantly associated with prognosis in malignant melanoma (MM) patients.
- CDCA1-specific siRNA inhibited melanoma cell proliferation but did not affect migration or invasion.
Conclusions:
- CDCA1 is frequently expressed in melanoma and serves as a potential prognostic marker.
- CDCA1 represents a promising novel therapeutic target for melanoma treatment.
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